The Effects of Metformin on Pregnancy and Miscarriage Rates in Polycystic Ovary Syndrome (PCOS)

NCT00994812 | Completed Phase 3

• 1 other identifier: T59108
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine whether metformin may improve pregnancy rates, and decrease miscarriage rates and complications of pregnancy, such as toxemia and gestational diabetes, in women with polycystic ovary syndrome (PCOS).

Conditions

Polycystic Ovary Syndrome; Miscarriage; Infertility; Toxemia; Gestational Diabetes

Keywords

Polycystic ovary syndrome; PCOS; Metformin; Miscarriage; Infertility; Complications of pregnancy

Outcome Measures

Primary Outcomes (1)

• Miscarriage rates

  at 7-8 weeks of pregnancy or later if miscarriage happens later

Secondary Outcomes (3)

• Effect of metformin versus placebo on the time to be pregnant

  3-6 months

• Effect of metformin versus placebo on the rates of toxemia during pregnancy

  3 months after birth of the child

• Effects of metformin versus placebo on the rates of gestational diabetes during pregnancy

  3 months after the birth of the child

Study Arms (1)

Metformin

EXPERIMENTAL

Drug: metformin

Interventions

metformin DRUG

The obese women will be randomized either to metformin (2g/day) or to placebo, and the non-obese either to metformin (1.5g/day) or to placebo. All subjects will be evaluated 1 to 7 days after spontaneous menstruation (oligomenorrheic patients), or at any other convenient time (amenorrheic subjects). After the treatment of 3 months with metformin/placebo alone, another appropriate infertility treatment will be combined with metformin/placebo (clomiphene, ovulation induction, insemination or in vitro fertilization) if no pregnancy has occurred. This treatment will be continued another 6 months' period. If pregnancy occurs, subjects will be re-examined at 7-8 weeks of gestation.

Metformin

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age \< 40 years at entry
• BMI \> 19 kg/m2
• Infertility lasting \> 1 year
• Criteria for PCOS are as defined by ESHRE/ASRM: at least two of the following findings:
• polycystic ovaries shown by vaginal ultrasonography (more than 12 subcapsular follicles of 3-8 mm diameter in one plane of the ovary)
• oligomenorrhea or amenorrhea
• clinical manifestations of hyperandrogenism such as a hirsutism score of \> 7 according to Ferriman and Gallwey (Ferriman \& Gallwey 1961)and/or an elevated serum testosterone level (\> 2.7 nmol/l).

You may not qualify if:

• diabetic subjects
• alcohol users
• active liver disease (ALAT \> +2 SD the upper normal value i.e.\> 100IU/l)
• hormonal drugs
• past or present cardiac failure (NYHA I-IV)
• liver or renal failure (S-Creatinine above the normal value ie.124 umol/l)
• pregnancy or lactation
• hypersensitivity to metformin

Sponsors & Collaborators

• University of Oulu: lead
• University of Eastern Finland: collaborator
• University of Helsinki: collaborator
• Tampere University: collaborator
• University of Turku: collaborator

Study Sites (5)

University Hospital Of Helsinki

Helsinki, Finland

Location

University Hospital of Kuopio

Kuopio, Finland

Location

University Hopsital of Oulu

Oulu, 90029, Finland

Location

University Hospital of Tampere

Tampere, Finland

Location

University Hospital of Turku

Turku, Finland

Location

Related Publications (9)

• Kashyap S, Wells GA, Rosenwaks Z. Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome. Hum Reprod. 2004 Nov;19(11):2474-83. doi: 10.1093/humrep/deh440. Epub 2004 Sep 9.

  PMID: 15358717 BACKGROUND

• Glueck CJ, Phillips H, Cameron D, Sieve-Smith L, Wang P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril. 2001 Jan;75(1):46-52. doi: 10.1016/s0015-0282(00)01666-6.

  PMID: 11163815 BACKGROUND

• Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril. 2002 Mar;77(3):520-5. doi: 10.1016/s0015-0282(01)03202-2.

  PMID: 11872206 BACKGROUND

• Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002 Feb;87(2):524-9. doi: 10.1210/jcem.87.2.8207.

  PMID: 11836280 BACKGROUND

• Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.

  PMID: 15840746 BACKGROUND

• Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66. doi: 10.1056/NEJMoa063971.

  PMID: 17287476 BACKGROUND

• Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006 Jun 24;332(7556):1485. doi: 10.1136/bmj.38867.631551.55. Epub 2006 Jun 12.

  PMID: 16769748 BACKGROUND

• Lingaiah S, Morin-Papunen L, Risteli J, Tapanainen JS. Metformin decreases bone turnover markers in polycystic ovary syndrome: a post hoc study. Fertil Steril. 2019 Aug;112(2):362-370. doi: 10.1016/j.fertnstert.2019.04.013. Epub 2019 Jun 18.

  PMID: 31227287 DERIVED

• Sova H, Puistola U, Morin-Papunen L, Karihtala P. Metformin decreases serum 8-hydroxy-2'-deoxyguanosine levels in polycystic ovary syndrome. Fertil Steril. 2013 Feb;99(2):593-8. doi: 10.1016/j.fertnstert.2012.10.013. Epub 2012 Oct 31.

  PMID: 23122829 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Abortion, Spontaneous; Infertility; Toxemia; Diabetes, Gestational; Pregnancy Complications

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Infections; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Laure C Morin-Papunen, PhD

  University hospital of Oulu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 14, 2009
• Study Start: August 1, 2002
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 23, 2010

Record last verified: 2009-10

Locations

FI (5)